11. News on PARP-1, Something More to Study
W. Lee Kraus, Pharmacology, Weill Cornell Medical College, and Molecular Biology and Genetics, and his research group discovered that an important cellular enzyme poly (ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in gene transcription, which could lead to new cancer and neurological disease therapies. The researchers have characterized a whole new activity for the long-studied protein. They found that PARP-1 converts DNA from an active to a silent state, which brings forth the question of what genes are affected and whether the genes that are up-regulated or down-regulated in a disease can be targeted with PARP-1 to turn the genes on or off. PARP-1 is the most abundantly expressed member of a family of proteins long known to be involved in the metabolism of nicotinamide adenine dinucleotide (NAD+), a cellular co-factor involved in both energy use and signaling within cells. By the manipulation of the NAD+/PARP-1 mechanism, scientists may find new pharmacological ways of switching genes on and off at will. In addition to the implications that PARP-1 may play a role in cancer, which is driven by genetic abnormalities, recent studies have found that inhibition of PARP-1 activity is associated with neurological and learning impairment, and it also has been implicated in immune responses, diabetes, and aging. There is the possibility that the NAD+/PARP-1 system may connect daily diet to genetic activity within cells.